Field of the Present Disclosure
The disclosure relates to animal brain imaging. Particularly, the disclosure relates to brain imaging on wake behaving animals.
Background Art
Brain imaging on small animals may be implemented through different methods but only a few of them enable researchers to study selected regions of the central nervous systems with a spatial and time resolution sufficient to image the function of neural structures.
Indeed, magnetic resonance imaging and scanner imaging methods generally result in low resolution images only enabling to access functional information relating to activated brain regions. Methods using electrodes directly inserted into the brain for analyzing brain electrical sensitivity are as far hindered by a severe precision requirement in positioning the electrodes and by a complex interpretation of the resulting electric signals.
Microscopy methods have proven useful in brain imaging. Brain slices microscopy on deceased animals is well known but in vivo microscopy on a living animal is a recent subject. Historically, in vivo microscopy could not analyze deep-brain regions as the technique lacks satisfactory resolution or because it requires over-invasive surgery. The Applicant has described an approach for functional fiber-optic imaging of the intact mouse brain (Vincent et al., Live imaging of neural structure and function by fibred fluorescence microscopy. EMBO reports September 2006). The Applicant showed that fibered fluorescence microscopy which uses a small-diameter fiber-optic probe to provide real-time images has a spatial resolution enabling to image various neural structures in the living animal. This method has been useful in many physiological studies requiring the in situ functional imaging of tissues in a living anaesthetized animal.
Recently, a growing need to obtain images on freely moving animals and to make available chronic studies has emerged. Freely moving animal imaging requires high stability for images acquisition. Stanford University researchers have developed a bundle microscopy technology mounted on a mouse skull using an adapted helmet that enables freely moving studies (High speed, miniaturized fluorescence microscopy in freely moving mice. Benjamin Flusberg et al. Nature Methods, October 2008). However, this technology requires large coring in the mouse's brain and thereby prohibits deep-brain insertion. Additionally, the considerable helmet weight bans a truly free movement and the images resolution level limits the precision of the technology. Recently, the Applicant disclosed (Maskos et al., Functional fibered fluorescence imaging in freely moving mouse, poster No. 598.8 disclosed during the 38th annual meeting of the Society for Neurosciences 2008) the use of a minimally invasive probe securely fixed to the head with dental cement for fiber-optic microscopy imaging of neuronal networks in behaving animals. However, in order to acquire images on an extended period for chronic studies, there is a need to recalibrate the imaging system, therefore requiring to extract the probe out of the brain of the animal and to place it back. According to the current method, extracting the probe presents risk of breaking the tip of the bundle, thereby excluding reusing the same animal to carry out the study and involving incompatible maintenance costs to polish the broken probe.
The Applicant proposes hereinunder an intracranial implant for positioning a fiber bundle probe in the brain of an animal. The Applicant also proposes a fiber bundle probe adapted to said implant, a stereotactic device to manipulate said implant and probe, and a method for brain fiber bundle microscopy.